Lipid bilayer membranes on solid supports are a widely studied model system to understand the structure and function of biological membranes. There are many applications of lipid bilayer membranes on solid supports, including but not limited to biosensors, biocompatible surface coatings, and targeted drug delivery systems. Self-assembly fabrication of lipid bilayer membranes taking advantage of liposome adsorption and spontaneous rupture on material substrates is popular, because the method does not require mechanical forces, occurs only at the solid-liquid interface, and is based on the diffusion-limited adsorption of liposomes onto the solid support. A wide range of experimental parameters influence the self-assembly process, including liposome properties (e.g., size, lipid composition, lamellarity and osmotic pressure), solution conditions (e.g., ionic strength, temperature, solution pH) and material properties (e.g., crystallinity, topology).
Traditionally, adjustment of electrostatic forces has been the primary aim of interfacial science approaches to tune lipid-substrate interactions but this approach is not always successful and the results are inconsistent. An example is the formation of a planar lipid bilayer on a solid support. On titanium oxide, formation of a planar bilayer by zwitterionic lipid vesicle adsorption and spontaneous rupture occurs at pH 4, which is below the isoelectric point (IEP) of titanium oxide (Tayebi, et al. Nature Materials 2012, Vol 11 pages 1074-1080). However, on aluminum oxide, formation of a planar bilayer by zwitterionic lipid vesicle adsorption and spontaneous rupture does not occur under the same pH condition, although the condition is also below the isoelectric point of aluminum oxide (Keller, et al. Biophysical Journal 1998, 75, (3), 1397-1402). Considering that, in both cases, there is electrostatic attraction between the negatively charged zwitterionic lipid vesicles and the positively charged substrates, the evidence supports that electrostatic attraction and methods to tune electrostatic forces are insufficient to form planar bilayers as a general means.
It is generally understood that the overall adhesion process depends on the material properties of the solid support. Liposomes typically adsorb and either remain intact (e.g., gold and titanium oxide) or rupture to form a planar bilayer (e.g., silicon oxide and mica). Groves et al. (Langmuir 1998, 14, (12), 3347-3350) have reported that several oxide film substrates may serve as barriers that prevent the self-assembly of lipid bilayer membranes, including aluminum oxide, which can hinder liposome adsorption. As some substrates may serve as barriers that prevent the self-assembly of lipid bilayer membranes, the range of solid supports that can be used to support lipid bilayers is quite narrow. Groves et al. identified Type I barriers such as aluminum oxide that can prevent vesicle adsorption, and Type II barriers such as indium tin oxide and chrome that support vesicle adsorption but the resulting bilayers are effectively immobile.
Several methods have been developed to form lipid bilayer membranes on solid supports which are intractable to liposome adsorption and spontaneous rupture, including covalently attaching auxiliary materials that facilitate adsorption and rupture of liposomes to the solid support. However, it has proven problematic to form a complete lipid bilayer membrane without adulterating the properties of the solid support or the lipid bilayer membrane through covalent modifications. These covalent modifications are time consuming, expensive and usually only work over small segments of the substrate.
Therefore, there is need in the art for strategies that overcome the limitations of existing support materials while circumventing the laborious and costly surface modification approach.
Furthermore, attempts to form lipid bilayer membranes on solid supports have only focused on the positive case, i.e., methods to form planar bilayers. There is also a need to develop methods to inhibit the formation of lipid bilayer membranes on solid supports tractable to vesicle adsorption and spontaneous rupture. As some materials adhere to cell membranes and lead to cell rupture, current nanoparticles and devices used in animals including humans are limited to a narrow range of materials that are not harmful to cells. This limitation makes the range of materials suitable for nanoparticles and devices for targeted drug delivery very narrow.
Accordingly, there is also need in the art for materials or methods that overcome the existing limitation in that the materials are imparted lipid rejecting properties.